The entourage effect is a proposed mechanism by which cannabis compounds other than tetrahydrocannabinol (THC) act synergistically with it to modulate the overall psychoactive effects of the plant.
Cannabis strains with relatively high CBD:THC ratios have been proposed to be less likely to induce anxiety than vice versa, though this assertion has been challenged on account of contradictory findings in the literature. This may be due to CBD's antagonistic effects at the cannabinoid receptors, compared to THC's partial agonist effect. CBD is also a 5-HT1A receptor (serotonin) agonist, which may also contribute to an anxiolytic-content effect. The effects of sativa are well known for its cerebral high, while indica is well known for its sedative effects which some prefer for night time use. Both types are used as medical cannabis.
The phrase entourage effect was introduced in 1999. While originally identified as a novel method of endocannabinoid regulation by which multiple endogenous chemical species display a cooperative effect in eliciting a cellular response, the term has evolved to describe the polypharmacy effects of combined cannabis phytochemicals or whole plant extracts. The phrase now commonly refers to the compounds present in cannabis supposedly working in concert to create "the sum of all the parts that leads to the magic or power of cannabis". Other cannabinoids, terpenoids, and flavonoids may be part of an entourage effect.
A 2020 review of research found no entourage effect in most studies, while other reports claimed mixed results, including the possibility of increased adverse effects. The review concluded that the term, "entourage effect", is unfounded and used mainly for marketing.
- Grof CP (November 2018). "Cannabis, from plant to pill". British Journal of Clinical Pharmacology. 84 (11): 2463–2467. doi:10.1111/bcp.13618. PMC 6177712. PMID 29701252.
- Russo EB (August 2011). "Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects". British Journal of Pharmacology. 163 (7): 1344–64. doi:10.1111/j.1476-5381.2011.01238.x. PMC 3165946. PMID 21749363.
- Hudson R, Renard J, Norris C, Rushlow WJ, Laviolette SR (October 2019). "Cannabidiol Counteracts the Psychotropic Side-Effects of Δ-9-Tetrahydrocannabinol in the Ventral Hippocampus through Bidirectional Control of ERK1-2 Phosphorylation". The Journal of Neuroscience. 39 (44): 8762–8777. doi:10.1523/JNEUROSCI.0708-19.2019. PMC 6820200. PMID 31570536.
- "Cannabis study reveals how CBD offsets the psychiatric side-effects of THC". ScienceDaily (Press release). September 30, 2019.
- Cogan PS (August 2020). "The 'entourage effect' or 'hodge-podge hashish': the questionable rebranding, marketing, and expectations of cannabis polypharmacy". Expert Review of Clinical Pharmacology. 13 (8): 835–845. doi:10.1080/17512433.2020.1721281. PMID 32116073. S2CID 211726166.
- Russo EB, Tyler VM (22 December 2015). Handbook of Psychotropic Herbs: A Scientific Analysis of Herbal Remedies for Psychiatric Conditions. Routledge. pp. 233–. ISBN 978-1-136-38607-7.
- "Marijuana Chemicals Cannabinoids, Terpenes, Flavonoids (THC and CBD)". Howtogrowmarijuana.com. 2015.
- Joy JE, Watson Jr SJ, Benson Jr JA (1999). Marijuana and Medicine: Assessing The Science Base. Washington D.C: National Academy of Sciences Press. ISBN 978-0-585-05800-9.
- Chen A (20 April 2017). "Some of the Parts: Is Marijuana's "Entourage Effect" Scientifically Valid?". Scientific American. Retrieved 2017-12-31.
- Fine PG, Rosenfeld MJ (2013-10-29). "The endocannabinoid system, cannabinoids, and pain". Rambam Maimonides Medical Journal. 4 (4): e0022. doi:10.5041/RMMJ.10129. PMC 3820295. PMID 24228165.
- Ben-Shabat S, Fride E, Sheskin T, Tamiri T, Rhee MH, Vogel Z, et al. (July 1998). "An entourage effect: inactive endogenous fatty acid glycerol esters enhance 2-arachidonoyl-glycerol cannabinoid activity". European Journal of Pharmacology. 353 (1): 23–31. doi:10.1016/s0014-2999(98)00392-6. PMID 9721036.
- Gupta S (11 March 2014). "Medical marijuana and 'the entourage effect'". CNN. Retrieved 31 December 2017.
- Russo EB (2019-01-09). "The Case for the Entourage Effect and Conventional Breeding of Clinical Cannabis: No "Strain," No Gain". Frontiers in Plant Science. 9: 1969. doi:10.3389/fpls.2018.01969. PMC 6334252. PMID 30687364.